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Biomedical subjects

J J Michiels

Publications and source records attributed to J J Michiels.

At least 73 records · Page 4Linked to original sources
PubMed1997

Aspirin in essential thrombocythemia: status quo and quo vadis.

Aspirin has a well established role in the prevention of arterial thrombosis. Discussion on the efficacy and safety of aspirin in the treatment and prophylaxis of thrombosis in essential thrombocythemia (ET) has become an important issue. The rationale for its use in ET comes from the observation that arterial thrombosis and platelet-mediated microcirculatory disturbances are the major causes of morbidity and mortality in ET. Experimental data have shown persistently elevated levels of thromboxane A2 (TXA2) in ET patients probably reflecting an enhanced in vivo platelet activation. Increased TXA2 biosynthesis and platelet activation in vivo in ET are selectively suppressed by repeated low doses of aspirin. ET-related symptoms such as erythromelalgia, transient neurologic and ocular disturbances are sensitive to aspirin. However, the benefit of low-dose aspirin is still uncertain in the primary prevention of thrombosis in ET. Furthermore, aspirin may unmask a latent bleeding diathesis frequently present in ET which may result in severe hemorrhagic complications. Thus, aspirin is contraindicated in ET patients with a bleeding history or a very high platelet count (> 1500 x 10(9)/L) leading to the acquisition of von Willebrand factor deficiency. If indicated, aspirin is presently used in the widely accepted low-dose regimen of 100 mg daily. However, an optimal effective dose has not yet been established. To further evaluate the efficacy and safety of aspirin in ET, prospective clinical trials are needed.

Abortion, Habitual↗
PubMed1997

The paradox of bleeding and thrombosis in thrombocythemia: is von Willebrand factor the link?

Thrombosis and bleeding, reflecting the extreme ends of hemostasis, are common complications in patients with thrombocythemia in its primary form or in association with polycythemia vera. The pathogenesis of these thrombohemorrhagic predispositions is not clearly understood. In the present study we describe the paradoxical and sequential occurrence of thrombotic and bleeding complications in six patients with thrombocythemia. Strikingly, in all patients some abnormality of plasma von Willebrand factor was detected. The potential role of von Willebrand factor in the pathogenesis of these hemostatic complications is discussed.

Aged↗
PubMed1997

Spontaneous erythroid colony formation as the clue to an underlying myeloproliferative disorder in patients with Budd-Chiari syndrome or portal vein thrombosis.

Budd-Chiari syndrome is a severe disease characterized by occlusion of large hepatic veins leading to death if untreated. Using the classical criteria for the diagnosis of polycythemia vera (PV), essential thrombocythemia (ET), and idiopathic myelofibrosis (IMF), overt PV was the underlying cause in about 10% of the cases and ET or IMF in only a very few. Using spontaneous endogenous erythroid colony (EEC) formation in vitro and/or bone marrow biopsies, a primary myeloproliferative disorder (PMD) was present in 78% of the patients with apparently idiopathic Budd-Chiari syndrome and in about half of the patients with portal, splenic, and/or mesenteric vein thrombosis. The diagnoses in 40 reported cases with hepatic vein thrombosis and spontaneous EEC were overt PV in 25 and latent unclassified PMD in 15 patients. The diagnoses of 40 reported cases with splanchnic vein thrombosis and spontaneous EEC were overt PV in 12, ET in 2, IMF in 2, and latent unclassified PMD with the presence of EEC in 24 patients. Thrombocytosis as a manifestation of myeloproliferative disease was recorded in 34 of 80 (42.5%) patients with spontaneous EEC and Budd-Chiari syndrome or portal vein thrombosis. Thrombocythemia was present in 15 of 41 patients with a proven and in 19 of 39 patients with a latent myeloproliferative disorder. Patients with hepatic vein or splanchnic vein thrombosis associated with a PMD are predominantly females younger than 45. It is concluded that both spontaneous EEC and histopathology from bone marrow biopsy provide specific information as sensitive clues to the diagnosis of all variants of overt and latent myeloproliferative disorders. The association of hepatic and splanchnic vein thrombosis and PMD is not fully understood. Therapeutic options of Budd-Chiari syndrome include anticoagulation with heparin, fibrinolysis followed by oral anticoagulation, and appropriate treatment of the underlying PMD. In case of failure, invasive options include local procedures such as angioplasty or stenting, venous decompression by portal-systemic shunts, or liver transplantation.

Biomarkers↗
PubMed1997

Erythromelalgia and vascular complications in polycythemia vera.

The vascular complications in patients with polycythemia vera are microvascular circulatory disturbances typical of thrombocythemia including erythromelalgia, peripheral ischemia, atypical cerebral ischemic attacks, and major arterial and venous thrombotic events. These are positively related to hematocrits due to the increased red cell mass and its concomitant increased whole blood viscosity. Phlebotomy does not prevent the aspirin-responsive microcirculatory circulation disturbances in polycythemia vera because thrombocythemia (platelet count > 400 x 10(9)/L) persists. The risk of major vascular ischemic episodes in poorly controlled polycythemia vera at hematocrits between 0.45 and 0.50 is rather high. The risk of vascular complications in polycythemia vera is best controlled by maintaining the hematocrit at less than 0.45 and the platelet count below 400 x 10(9)/L. The microvascular syndrome associated with thrombocythemia in early stage polycythemia vera in remission by phlebotomy is easily and best controlled by low-dose aspirin (50 to 100 mg) or by selective reduction of platelet count to normal with low-dose myelosuppressive agents. The potential leukemogenic myelosuppressive agents busulfan and hydroxyurea and the nonleukemogenic cytosine interferon-alpha have proven to be effective in the control of the proliferative phase of polycythemia vera. However, data on the natural history of polycythemia vera and the best treatment modality of the various stages of myeloproliferative disease are still lacking.

Aspirin↗
PubMed1997

Acquired haemophilia A in women postpartum: management of bleeding episodes and natural history of the factor VIII inhibitor.

The present study reports on the treatment of bleeding episodes and the natural history of factor VIII inhibitors in 4 patients with acquired haemophilia A postpartum. Low titre type II factor VIII inhibitors in 3 patients and high titre type I inhibitor in 1 patient became apparent immediately to 7 months after delivery. High dose human factor VIII concentrate substitution was effective in controlling bleeding episodes in two cases of factor VIII inhibitor type II, but ineffective in 1 patient with high titre type I factor VIII inhibitor. High dose gammaglobulin intravenously in 1 patient with type II factor VIII inhibitor induced a partial correction of factor VIIIc levels for 2 wk. Immunosuppressive treatment in all 4 patients with acquired haemophilia A postpartum did not reduce the potency of the factor VIII inhibitors. The low titre type II inhibitors spontaneously disappeared in all 3 patients within a few months to 1 yr after discontinuation of the immunosuppressive treatment. The high titre type I factor VIII inhibitor persisted for more than 24 yr. We conclude that immunosuppression in 4 women with acquired haemophilia A postpartum did not significantly affect the factor VIII inhibitor titre.

Adult↗
PubMed1996

Vertebral bone destruction in sickle cell disease: infection, infarction or both.

Infectious and vaso-occlusive vertebral bone and joint destruction in two patients with sickle cell disease (SCD) are featured by H-shaped vertebrae, kyphotic angulation, osteolysis of endplates and collapse of intervertebral discs as shown by X-ray films and magnetic resonance imaging. Staphylococcal serology supported the diagnosis of staphylococcal osteomyelitis/spondylo-discitis in both SCD patients. The difficulties of establishing the causes and treatment of the osteoarthropathy in these particular cases are discussed in the light of the literature.

Adult↗
PubMed1996

The reduction of large von Willebrand factor multimers in plasma in essential thrombocythaemia is related to the platelet count.

We have investigated the relationship between platelet count and large VWF (von Willebrand factor) multimers in the plasma of 36 patients with essential thrombocythaemia (ET) and 26 patients with reactive thrombocytosis (RT). In both ET and RT patients an inverse relationship could be established between platelet count and large VWF multimers in plasma as well in relatively decreased ristocetin cofactor/von Willebrand factor antigen and collagen binding activity/von Willebrand factor antigen ratios. A normalization of the platelet count was accompanied by restoration of a normal plasma VWF multimeric distribution. Our data suggest that increasing numbers of platelets circulating in blood result in increased removal of large VWF multimers from plasma.

Adult↗
PubMed1996

Cutaneous pathology in primary erythermalgia.

Primary or idiopathic erythermalgia is characterized by recurrent, red, warm, and painful lower extremities. It arises at young age and persists throughout life because no treatment is available. We report the cutaneous pathology of affected skin lesions of three patients with primary erythermalgia. Biopsy specimens showed a mild perivascular mononuclear infiltrate, thickened blood vessel basement membranes, abundant perivascular edema, and moderate endothelial swelling. The thickened basal membrane of the blood vessels showed a laminar structure, and abundant perivascular edema and moderate endothelial cell swelling were evident. These histopathologic findings in primary erythermalgia appear to be nonspecific but allow diagnostic differentiation from erythromelalgia in which fibromuscular intimal proliferation and occlusive thrombi in the endarteriolar capillaries are apparent and from erythermalgia secondary to vasculitis. Histopathologic examination of affected skin lesions in patients with red, congested, warm, and painful burning extremities is a valuable tool in the diagnostic process.

Adolescent↗
PubMed1996

Heparin-induced thrombocytopenia with multiple cerebral infarctions simulating thrombotic thrombocytopenic purpura. A case report.

The authors describe a patient with stroke, treated with heparin for unstable angina, whose clinical features mimicked those of thrombotic thrombocytopenic purpura (TTP). His condition eventually proved to be caused by heparin-induced thrombocytopenia (HIT), complicated by thrombosis (HITT). The absence of microangiopathic hemolytic anemia should question the diagnosis in a presumed TTP patient. Early diagnosis of HITT is possible since recently two highly sensitive and specific tests have become available. Heparin treatment has to be stopped immediately if HITT is diagnosed. First-choice antithrombotic treatment in HITT patients is danaparoid.

Anticoagulants↗
PubMed1996

The myeloproliferative disorders. An historical appraisal and personal experiences.

According to strict morphological, biochemical and cytogenetic criteria Philadelphia chromosome positive essential thrombocythemia and chronic granulocytic leukemia constitute a separate malignant and individual disease entity, whereas Philadelphia chromosome negative essential thrombocythemia, polycythemia vera and agnogenic or megakaryocytic myeloid metaplasia form a chronic proliferation of three hematopoietic cell lines. Histopathology from bone marrow biopsies permits the characterization and diagnostic differention of the various myeloproliferative disorders and appears to be a main and specific diagostic criterion for polycythemia vera and essential thrombocythemia. Hemorrhagic thrombocythemia is a clinical syndrome of recurrent spontaneous mucocutaneous and secondary hemorrhages often preceded by thromboses, extremely high platelet counts, pseudohyperkalemia, increased bone marrow cellularity and frequently splenomegaly. The diagnostic criteria of essential thrombocythemia with paradoxical occurrence of thrombotic events and hemorrhagic manifestations are a platelet count in excess of 1000 x 10(9)/L and increased bone marrow cellularity in the majority of the cases. Erythromelalgia and other microcirculatory ischemic or thrombotic events or accidents in essential thrombocythemia and polycythemia vera already occur at platelet counts in excess of the upper limit of normal. First line treatment options in essential thrombocythemia and polycythemia vera are control of platelet function with low-dose aspirin and reductive control of platelet count and erythrocytes by bloodletting, interferon and busulfan or hydroxyurea monochemotherapy.

Bone Marrow↗
PubMed1996

Erythromelalgic, thrombotic and hemorrhagic manifestations in 50 cases of thrombocythemia.

Fifty consecutive patients with thrombocythemia (35 men and 15 women) were diagnosed as primary thrombocythemia (PT) in 30 and thrombocythemia associated with polycythemia vera (PV) in 20. The symptoms were platelet-mediated erythromelalgia in 16 PT and 15 PV, coronary artery disease in 3 PT and 2 PV, atypical cerebral ischemic attacks in 8 PT and 3 PV, paradoxical thrombosis and bleeding in 3 PT and 2 PV and hemorrhages alone in 6 PT and 2 PV patients. Erythromelalgia was localized in the forefoot sole and toes in 28, the fingertips in 9, the handpalm in 2. Untreated erythromelalgia progressed to acrocyanosis or peripheral ischemia with necrosis in a toe or fingertip in 14 cases. Painful red, warm and indurated erythromelalgic hot spots in the skin of the upper legs were misdiagnosed as superficial thrombophelebitis in 5 PT and 2 PV patients. Erythromelalgia in thrombocythemia already occurred at slightly increased platelet counts above 400 x 10(9)/l. The curative effect of aspirin on erythromelalgia in thrombocythemia was consistently accompanied by a significant increase of platelet counts. Erythromelalgia and bleeding paradoxically occurred in 5 patients at platelet counts between 1000 and 2000 x 10(9)/l. In this situation aspirin prevents erythromelalgic and microcirculatory circulation disturbances, but further increases the risk of serious bleeding complications. Presenting hemorrhagic manifestations in thrombocythemia were observed at platelet counts in excess of 1000 x 10(9)/l in 9 PT and 4 PV patients as severe epistaxis in 5, atypical ecchymoses in 3, gastrointestinal bleeding in 2 and secondary bleeding in 3. The concept of platelet-mediated erythromelalgia, thrombosis and hemorrhages in thrombocythemia is discussed.

Adult↗
PubMed1996

Atypical transient ischemic attacks in thrombocythemia of various myeloproliferative disorders.

Neurological symptoms of transient unsteadiness, dysarthria, dysphasia, dysbasia, transient monoor hemiparesis, hemiparesis, scintillating scotomas, amaurosis fugax, vertigo, dizziness, migraine accompaniments, syncope and seizures were the presenting manifestations of thrombocythemia in various myeloproliferative disorders. Erythromelalgia preceded or followed the neurologic ischemic attacks. The neurologic and ocular attacks usually had a sudden onset, lasted for a few seconds to several minutes and occurred independently or sequentially rather than simultaneously. This clinical syndrome is caused by platelet-mediated ischemic and thrombotic processes in the end-arterial microvasculature and reflects the existence of a platelet dependent and aspirin responsive arterial thrombophilia in thrombocythemia as novel disease entity, which confirms and elucidates Mitchell's hypothesis.

Adult↗
PubMed1996

Bleeding time and platelet function in essential thrombocythemia and other myeloproliferative syndromes.

Bleeding time (BT) and platelet function tests have been widely used in patients with essential thrombocythemia (ET), with the aim to support diagnosis and to identify laboratory predictors of haemorrhagic and thrombotic complications. BT is significantly prolonged in 7-19% of ET patients and several functional abnormalities have been observed in platelet structure, biochemistry and survival. However, the attempt to relate these in vivo and in vitro platelet dysfunctions with diagnosis or clinical sequelae has been generally disappointing. Therefore, BT and platelet function tests are currently not recommended in the initial evaluation or during the follow-up of patients with ET, unless in the setting of a clinical or biological study. A noteworthy exception is represented by a subset of patients characterized by very high platelet count (> 1500 x 10(9)/L) and bleeding symptoms, who can have an acquired von Willebrand disease. In these cases, prolonged BT and abnormal multimeric pattern of von Willebrand factor are useful for diagnosing and monitoring this acquired hemorrhagic disease. BT and platelet function tests should be included in the baseline evaluation of ET patients enrolled in prospective clinical trials aiming assess their predictive role on clinical end-points.

Arachidonic Acid↗
PubMed1996

Acquired von Willebrand disease in myeloproliferative disorders.

The laboratory features of acquired von Willebrand defect (AvWD) in myeloproliferative disorders (MPD) are characterized by a very high platelet count, a normal or prolonged bleeding time, a normal factor VIII and von Willebrand factor (vWF) antigen level, but a decreased vWF-ristocetine cofactor activity and collagen binding activity with a decrease or absence of large vWF-multimers simulating a type II von Willebrand factor deficiency. Although the pathogenesis of type II AvWD in MPD remains unclear, evidence is accumulating that the increased number of platelets in the circulating blood seems to be directly responsible for the observed decrease of large vWF-multimers in plasma leading to a spontaneous bleeding tendency at very high platelet counts. This observation may have clinical implications for the use of platelet anti-aggregants such as aspirin in MPD at platelet counts in excess of 1000 to 2000 x 10(9)/L.

Aspirin↗
PubMed1996

Phenotyping and genotyping of coagulation factor V Leiden.

The currently used activated Protein C resistance test demonstrated to be of limited diagnostic value for the detection of the mutant Factor V Leiden. Moreover, this assay is not useful for patients under anticoagulant therapy. A modification of the APC resistance test, applying Factor V deficient plasma is described which demonstrates a specificity and sensitivity of 1.0. The superiority of the modified APC resistance test over the existing APC resistance test was verified by genotyping. For that purpose, the Amplification Refractory Mutation System (ARMS) was applied to the detection of the G to A mutation at position 1691 in the gene encoding coagulation Factor V. The mutation at that position could be easily detected by using each of two allele-specific oligonucleotide primers concomitantly with one common primer in two separate polymerase chain reactions, thereby amplifying a fragment of 186 base-pairs of the Factor V gene.

Base Sequence↗